Two roles for the Drosophila IKK complex in the activation of Relish and the induction of antimicrobial peptide genes
Two roles for the Drosophila IKK complex in the activation of Relish and the induction of antimicrobial peptide genes
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DOI：
10.1073/pnas.0812022106
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发表时间：
2009-06-16
影响因子：
11.1
通讯作者：
Silverman, Neal
中科院分区：
文献类型：
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作者：
Erturk-Hasdemir, Deniz;Broemer, Meike;Silverman, Neal
果蝇核因子-kappaB转录因子RAISE是革兰氏阴性菌感染后抗菌肽基因诱导的重要调控因子。AREISH是一个两段的核因子-kappaB前体蛋白，其N-端有一个Rel同源结构域，C-端有一个I-kappa B样结构域，类似于哺乳动物的P100和P105。与这些哺乳动物的同源物不同，ARISH在感染后被内切蛋白切割，允许N端的NF-kappa B模块移位到细胞核。信号依赖的味觉激活，包括切割，既需要果蝇I kappa B激酶(Ikk)，也需要死亡相关的ce-3/Nedd2样蛋白(Dredd)，即果蝇caspase-8样蛋白酶。在这份报告中，我们表明IKK复合体通过丝氨酸528和529上的直接磷酸化来控制美味。令人惊讶的是，这些磷酸化位点并不是美味分裂、核转位或DNA结合所必需的。相反，它们对RNA聚合酶II的募集和抗菌肽基因的诱导至关重要，而IKK则非催化地支持Dredd介导的调味品切割。
The Drosophila NF-kappa B transcription factor Relish is an essential regulator of antimicrobial peptide gene induction after Gram-negative bacterial infection. Relish is a bipartite NF-kappa B precursor protein, with an N-terminal Rel homology domain and a C-terminal I kappa B-like domain, similar to mammalian p100 and p105. Unlike these mammalian homologs, Relish is endoproteolytically cleaved after infection, allowing the N-terminal NF-kappa B module to translocate to the nucleus. Signal-dependent activation of Relish, including cleavage, requires both the Drosophila I kappa B kinase (IKK) and death-related ced-3/Nedd2-like protein (DREDD), the Drosophila caspase-8 like protease. In this report, we show that the IKK complex controls Relish by direct phosphorylation on serines 528 and 529. Surprisingly, these phosphorylation sites are not required for Relish cleavage, nuclear translocation, or DNA binding. Instead they are critical for recruitment of RNA polymerase II and antimicrobial peptide gene induction, whereas IKK functions noncatalytically to support Dredd-mediated cleavage of Relish.